PMID- 31175545
OWN - NLM
STAT- MEDLINE
DCOM- 20210111
LR  - 20210111
IS  - 1699-3055 (Electronic)
IS  - 1699-048X (Linking)
VI  - 22
IP  - 4
DP  - 2020 Apr
TI  - The effect of fenofibrate, a PPARalpha activator on toll-like receptor-4 signal 
      transduction in melanoma both in vitro and in vivo.
PG  - 486-494
LID - 10.1007/s12094-019-02150-7 [doi]
AB  - BACKGROUND: The anti-cancer effect of peroxisome proliferator-activated receptor 
      (PPAR) alpha ligands on growth and metastatic potential of melanoma cells has been 
      shown previously. However, the mechanism underlying these effects remains to be 
      elucidated. Here, we investigated the effects of fenofibrate (PPAR ligand) on 
      Toll-like receptor-4 (TLR-4) signaling in mice melanoma. METHODS: Mice melanoma 
      cells (B16F10) were treated with fenofibrate or LPS or LPS + fenofibrate or 
      pre-treated with CLI-095 (a TLR4 inhibitor), followed by fenofibrate. In in vivo 
      model, C57BL/6 mice were subcutaneously injected with B16F10 cells (with/without 
      LPS pre-treatment), and fenofibrate was administrated after development of 
      palpable tumors. Cell proliferation, the expression level of Tlr4, Myd88, Nf-kappab1 
      genes, TLR-4 protein expression, TNF-alpha levels, and tumor volume were measured. 
      RESULT: Our results indicated that fenofibrate significantly inhibited the Tlr-4, 
      Myd-88, and Nf-kb1 mRNA expression and TNF-alpha concentration in B16F10 
      LPS-stimulated cells. In addition, blocking TLR-4 signaling increased the 
      anti-inflammatory potential of fenofibrate. Also fenofibrate can reduce 
      LPS-induced tumor volume, Tlr-4, Myd-88, Nf-kb1 mRNA, and TLR-4 protein 
      expression in tumor tissue and also TNF-alpha level in tumor tissue lysate. 
      CONCLUSION: Our data indicate that fenofibrate may exert its anti-melanoma 
      effects via interaction with TLR4-dependent signaling pathway (TLR-4/MyD-88/ 
      NF-kB).
FAU - Dana, N
AU  - Dana N
AD  - Applied Physiology Research Center and Department of Physiology, Cardiovascular 
      Research Institute, Isfahan University of Medical Sciences, Isfahan, Iran.
FAU - Haghjooy Javanmard, S
AU  - Haghjooy Javanmard S
AD  - Applied Physiology Research Center and Department of Physiology, Cardiovascular 
      Research Institute, Isfahan University of Medical Sciences, Isfahan, Iran.
FAU - Vaseghi, G
AU  - Vaseghi G
AUID- ORCID: 0000-0003-3040-6135
AD  - Applied Physiology Research Center and Department of Physiology, Cardiovascular 
      Research Institute, Isfahan University of Medical Sciences, Isfahan, Iran. 
      golnazvaseghi@yahoo.com.
AD  - Isfahan Cardiovascular Research Center, Cardiovascular Research Institute, 
      Isfahan University of Medical Sciences, Isfahan, Iran. golnazvaseghi@yahoo.com.
LA  - eng
GR  - 95844116/Iran National Science Foundation/
PT  - Journal Article
DEP - 20190607
PL  - Italy
TA  - Clin Transl Oncol
JT  - Clinical & translational oncology : official publication of the Federation of 
      Spanish Oncology Societies and of the National Cancer Institute of Mexico
JID - 101247119
RN  - 0 (Myd88 protein, mouse)
RN  - 0 (Myeloid Differentiation Factor 88)
RN  - 0 (NF-kappa B)
RN  - 0 (PPAR alpha)
RN  - 0 (Sulfonamides)
RN  - 0 (Tlr4 protein, mouse)
RN  - 0 (Toll-Like Receptor 4)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (ethyl 6-(N-(2-chloro-4-fluorophenyl)sulfamoyl)cyclohex-1-ene-1-carboxylate)
RN  - U202363UOS (Fenofibrate)
SB  - IM
MH  - Animals
MH  - Cell Line, Tumor
MH  - Fenofibrate/*pharmacology
MH  - Melanoma/*drug therapy
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Myeloid Differentiation Factor 88/genetics
MH  - NF-kappa B/antagonists & inhibitors/genetics
MH  - PPAR alpha/*agonists
MH  - Signal Transduction/drug effects
MH  - Sulfonamides/pharmacology
MH  - Toll-Like Receptor 4/analysis/antagonists & inhibitors/genetics/*physiology
MH  - Tumor Necrosis Factor-alpha/pharmacology
OTO - NOTNLM
OT  - Melanoma
OT  - PPAR alpha
OT  - Toll-like receptor-4
EDAT- 2019/06/09 06:00
MHDA- 2021/01/12 06:00
CRDT- 2019/06/09 06:00
PHST- 2019/03/02 00:00 [received]
PHST- 2019/05/29 00:00 [accepted]
PHST- 2019/06/09 06:00 [pubmed]
PHST- 2021/01/12 06:00 [medline]
PHST- 2019/06/09 06:00 [entrez]
AID - 10.1007/s12094-019-02150-7 [pii]
AID - 10.1007/s12094-019-02150-7 [doi]
PST - ppublish
SO  - Clin Transl Oncol. 2020 Apr;22(4):486-494. doi: 10.1007/s12094-019-02150-7. Epub 
      2019 Jun 7.